Iodine → 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile

HRID 2388515Notes

Reaction equation

HRID 2388515 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II.CCN(CC)CC.[Si:29]([O:36][C@@H:37]([CH3:65])[C@@H:38]([NH:53][C:54]1[C:62]2[CH:61]=[CH:60][S:59][C:58]=2[C:57]([C:63]#[N:64])=[CH:56][CH:55]=1)[C:39]([NH:41][NH:42][C:43](=O)[C:44]1[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=1)=[O:40])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]>C(Cl)Cl>[Si:29]([O:36][C@@H:37]([CH3:65])[C@@H:38]([NH:53][C:54]1[C:62]2[CH:61]=[CH:60][S:59][C:58]=2[C:57]([C:63]#[N:64])=[CH:56][CH:55]=1)[C:39]1[O:40][C:43]([C:44]2[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=2)=[N:42][N:41]=1)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 807Iodine2×HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 67006558N'-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(7-cyanobenzo[b]thiophen-4-ylamino)butanoyl)-4-cyanobenzohydrazide

Product 1

HCID 670061894-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrileYield 98.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of triphenylphosphine (275 mg, 1.43 mmol) in DCM (24 mL) was added I2 (363 mg, 1.43 mmol) at 0° C. After I2 was dissolved completely, Et3N (0.40 mL, 2.87 mmol) was added, followed by a solution of N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(7-cyanobenzo[b]thiophen-4-ylamino)butanoyl)-4-cyanobenzohydrazide (380 mg, 0.71 mmol) in DCM (12 mL). After addition, the reaction mixture was allowed to warm to room temperature and stirred for additional 10 min. The reaction was quenched with saturated sodium thiosulfate (3 mL) and diluted with DCM (100 mL). The organic layer was separated and washed with water, brine and dried over Na2SO4. Removal of the solvent gave a residue, which was purified by flash chromatography to provide the title compound 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile (360 mg, 98%). 1H NMR (400 MHz, CDCl3, δ in ppm) 8.22 (d, J=8.4 Hz, 2H), 7.93 (d, J=8.4 Hz, 2H), 7.73 (d, J=5.5 Hz, 1H), 7.68 (d, J=8.2 Hz, 1H), 7.55 (d, J=5.5 Hz, 1H), 6.63 (d, J=8.2 Hz, 1H), 5.89 (d, J=8.6 Hz, 1H), 5.12 (m, 1H), 4.74 (m, 1H), 1.61 (d, J=6.2 Hz, 3H), 1.05 (s, 9H), 0.26 (s, 3H), 0.00 (s, 3H).

Workup

  1. additionAfter addition
  2. customThe reaction was quenched with saturated sodium thiosulfate (3 mL)
  3. additiondiluted with DCM (100 mL)
  4. customThe organic layer was separated
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent
  8. customgave a residue, which
  9. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-a9bf0ed879804103aff2ffc54065b259
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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